NEW YORK--A novel nucleoside analog has demonstrated clinical
benefits measured by reduction in pain, weight gain, and an improvement
in performance status in patients with advanced pancreatic cancer.
Gemcitabine (Gemzar) has shown a broad spectrum of activity against
a range of solid tumors in both preclinical and clinical studies,
Howard A. Burris III, MD, reported at the 13th annual symposium
of the Chemotherapy Foundation.
In phase I and II trials of patients with advanced pancreatic
cancer, gemcitabine produced only modest response rates (in the
range of 11%), said Dr. Burris, associate professor and director
of Drug Development, Brooke Army Medical Center, Cancer Therapy
and Research Center, San Antonio.
Improvements in disease-related symptoms, however, have been far
greater, Dr. Burris said, as have correlative improvements in
performance status, weight gain, and pain control. These observations
led to the development of a clinical benefit endpoint to be used
in the prospective evaluation of gemcitabine in pancreatic cancer.
Dr. Burris described two trials in which clinical benefit endpoints
were assessed in terms of pain (composite of analgesic consumption
and pain intensity), performance status (an improvement of 20
or more points on the Karnofsky scale), and weight gain (7% or
more over baseline), all over the course of 4 weeks or longer.
In the first trial, 126 patients were randomized to receive gemcitabine
(1,000 mg/m²) or fluorouracil (600 mg/m²) as a 30-minute
weekly infusion. Clinical benefit response was 23.8% among gemcitabine
patients, compared with 4.8% for those receiving fluorouracil.
Median survival was 5.65 months for patients receiving gemcitabine
versus 4.41 months for those on fluorouracil. Among gemcitabine
patients, 18% were alive at 1 year, compared with 2% of fluorouracil